A 127-kDa protein (UV-DDB) binds to the cytoplasmic domain of the Alzheimer's amyloid precursor protein

Takuo Watanabe, Jun Sukegawa, Izumi Sukegawa, Susumu Tomita, Ko Ichi Iijima, Shinobu Oguchi, Toshiharu Suzuki, Angus C. Nairn, Paul Greengard

研究成果: Article査読

43 被引用数 (Scopus)

抄録

Alzheimer amyloid precursor protein (APP) is an integral membrane protein with a short cytoplasmic domain of 47 amino acids. It is hoped that identification of proteins that interact with the cytoplasmic domain will provide new insights into the physiological function of APP and, in turn, into the pathogenesis of Alzheimer's disease. To identify proteins that interact with the cytoplasmic domain of APP, we employed affinity chromatography using an immobilized synthetic peptide corresponding to residues 645-694 of APP695 and identified a protein of ~130 kDa in rat brain cytosol. Amino acid sequencing of the protein revealed the protein to be a rat homologue of monkey UV-DDB (UV-damaged DNA-binding protein, calculated molecular mass of 127 kDa). UV-DDB/p127 co-immunoprecipitated with APP using an anti-APP antibody from PC12 cell lysates. APP also coimmunoprecipitated with UV-DDB/p127 using an anti-UV-DDB/p127 antibody. These results indicate that UVDDB/p127, which is present in the cytosolic fraction, forms a complex with APP through its cytoplasmic domain. In vitro binding experiments using a glutathione S-transferase-APP cytoplasmic domain fusion protein and several mutants indicated that the YENPTY motif within the APP cytoplasmic domain, which is important in the internalization of APP and amyloid β protein secretion, may be involved in the interaction between UV- DDB/p127 and APP.

本文言語English
ページ(範囲)549-556
ページ数8
ジャーナルJournal of Neurochemistry
72
2
DOI
出版ステータスPublished - 1999

ASJC Scopus subject areas

  • 生化学
  • 細胞および分子神経科学

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